Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously defined viability limits in a rat transplantation model. All liver allografts stored in a simple preservation solution (NaCl 0.9%, CaCl2 2 mM) at 4 degrees C for 4 hr or at 37 degrees C for 1 hr were viable upon transplantation, but all those stored at 4 degrees C for 8 hr or at 37 degrees C for 2 hr were nonviable. Only cold-preserved, nonviable livers showed increased vascular resistance, platelet trapping and an initially low, but then high, rise in aspartate transaminase (AST) upon reperfusion, all suggesting injury to the microcirculation, with secondary injury to the hepatocyte. In the present study, we investigated the morphological changes that occur in livers stored for the defined critical times, using light and electron microscopy after perfusion-fixation. Accurate and reproducible identification of specimens as belonging to viable or nonviable and warm- or cold-preserved could be made in this way. Preservation in the cold first resulted in reversible changes consisting of cellular swelling, alterations of intracellular organelles, and partial denudation of the sinusoidal lining (cold-preserved viable group). Later, under conditions of nonviable cold preservation, detachment of cell bodies of sinusoidal lining cells with nuclear changes and almost complete denudation of the sinusoidal lining was observed. Endothelial cells of larger vessels were only injured mildly. In contrast, under conditions of warm preservation, changes involving mitochondria and later nuclei were found in hepatocytes, and blebbing was more extensive. Endothelial cells were spared relatively. We also examined livers stored in isotonic citrate solution at 4 degrees C for 8 hr and 16 hr, the critical times determined for this solution in another model of rat liver transplantation. The findings were very similar to storage in saline with respect to the changes in the sinusoidal lining cells after cold preservation for the two critical times. The results provide convincing evidence of a qualitative difference between warm and cold preservation injury, with relatively selective damage to hepatocytes or sinusoidal lining cells, respectively. Endothelial damage represents the primary event, resulting in the loss of organ viability following hypothermic storage. Thus morphology may serve as a useful viability marker after preservation.
 ...
PMID:Sinusoidal lining cell damage: the critical injury in cold preservation of liver allografts in the rat. 304 74

The aim of this study was to determine whether calcium potentiates acute carbon tetrachloride (CCl4) -induced toxicity. Elevated calcium levels were induced in mice by pre-treatment with cholecalciferol (vitamin D3; V.D3), a compound that has previously been shown to induce hypercalcemia in human and animal models. As seen previously, mice injected with CCl4 exhibited increased plasma levels of alanine aminotransferase, aspartate aminotransferase, and creatinine; transient body weight loss; and increased lipid peroxidation along with decreased total antioxidant power, glutathione, ATP, and NADPH. Pre-treatment of these animals with V.D3 caused further elevation of the values of these liver functional markers without altering kidney functional markers; continued weight loss; a lower lethal threshold dose of CCl4; and enhanced effects on lipid peroxidation and total antioxidant power. In contrast, exposure to V.D3 alone had no effect on plasma markers of liver or kidney damage or on total antioxidant power or lipid peroxidation. The potentiating effect of V.D3 was positively correlated with elevation of hepatic calcium levels. Furthermore, direct injection of CaCl2 also enhanced CCl4-induced hepatic injury. Since CaCl2 induced hypercalcemia transiently (within 3 h of injection), our results suggest that calcium enhances the CCl4-induced hepatotoxicity at an early stage via potentiation of oxidative stress.
 ...
PMID:Vitamin D3-induced hypercalcemia increases carbon tetrachloride-induced hepatotoxicity through elevated oxidative stress in mice. 2844 45